Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma.

Academic Article

Abstract

  • To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.

    • Authors

    Published In

  • Cell  Journal

    • Keywords

  • CPTAC, ccRCC, chromosomal translocation, drug targets, immune infiltration, phosphoproteomics, proteogenomics, proteomics, renal carcinoma, tumor microenvironment, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Renal Cell, Disease-Free Survival, Exome, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Humans, Male, Middle Aged, Neoplasm Proteins, Oxidative Phosphorylation, Phosphorylation, Proteogenomics, Signal Transduction, Transcriptome, Tumor Microenvironment, Exome Sequencing

    • Digital Object Identifier (doi)

    Author List

  • Clark DJ; Dhanasekaran SM; Petralia F; Pan J; Song X; Hu Y; da Veiga Leprevost F; Reva B; Lih T-SM; Chang H-Y

    • Start Page

  • 964

    • End Page

  • 983.e31

    • Volume

  • 179

    • Issue

  • 4